title: Highly polymorphic promoter regions of HLA DQA1 and DQB1 genes do not help to further define disease susceptibility in insulin-dependent diabetes mellitus.
abstract: HLA DQA1, HLA DQB1 genes confer susceptibility to insulin-dependent (type 1) diabetes mellitus (IDDM). Since variants of their upstream regulatory regions are linked to the exons, we investigated their promoter polymorphisms (QAP and QBP) by a combination of PCR-based typing protocols in 136 IDDM patients, 167 controls and 6 families with an IDDM proband to identify possible additional susceptibility markers. Of major interest for IDDM susceptibility are the promoter "splits" of HLA DQA1*0301 (QAP3.1 and QAP3.2) and HLA DQB1*0302 (QBP3.2 and QBP3.3). QAP 3.1 (96% in patients vs 98% in controls) and QBP3.2 (100% vs 99%) were found to be the most frequent promoter variants for HLA DQA1*0301 and DQB1*0302, respectively, whereas QAP3.2 and QBP3.3 were very rare. Furthermore the promoter "splits" were equally distributed on the respective exon alleles in all groups and cosegregated in families as expected. In conclusion, HLA DQ-mediated susceptibility and protection in IDDM is not restricted to the exon but extends to the promoter region without further defining the genetic risk.
authors.affiliation: Medical Department I, Center of Internal Medicine, Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Donner
authors.forename: H
authors.initials: H
authors.lastname: Rau
authors.forename: J
authors.initials: J
authors.lastname: Braun
authors.forename: J
authors.initials: J
authors.lastname: Herwig
authors.forename: K H
authors.initials: KH
authors.lastname: Usadel
authors.forename: K
authors.initials: K
authors.lastname: Badenhoop
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006801:Humans; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen